PUF60

poly(U) binding splicing factor 60, the group of RNA binding motif containing|Spliceosomal A complex

Basic information

Region (hg38): 8:143816343-143830709

Links

ENSG00000179950 ∙ NCBI:22827 ∙ OMIM:604819 ∙ HGNC:17042 ∙ Uniprot:Q9UHX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 8q24.3 microdeletion syndrome (Strong), mode of inheritance: AD
• 8q24.3 microdeletion syndrome (Strong), mode of inheritance: AD
• 8q24.3 microdeletion syndrome (Definitive), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Verheij syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Ophthalmologic; Renal	19464398; 24140112
There is evidence that the condition may result from a deletion of multiple genes including PUF60 as well as heterozygous pathogenic variants in PUF60 alone

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PUF60 gene.

• not provided (89 variants)
• 8q24.3 microdeletion syndrome (60 variants)
• Inborn genetic diseases (16 variants)
• not specified (2 variants)
• PUF60-related condition (2 variants)
• CHARGE association (1 variants)
• Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome (1 variants)
• See cases (1 variants)
• Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PUF60 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				16	2	18
missense		13	36	3	1	53
nonsense	8	4				12
start loss						0
frameshift	21	13				34
inframe indel		1	3	2		6
splice donor/acceptor (+/-2bp)	3	6	2			11
splice region			4	2		6
non coding			1	2	2	5
Total	32	37	42	23	5

Variants in PUF60

This is a list of pathogenic ClinVar variants found in the PUF60 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-143816521-C-G			Uncertain significance (Dec 08, 2022)
8-143816524-G-A		Inborn genetic diseases	Uncertain significance (Dec 12, 2023)
8-143816525-CAG-C		Neurodevelopmental abnormality • PUF60-related disorder	Uncertain significance (Feb 16, 2024)
8-143816542-T-C		Intellectual disability-cardiac anomalies-short stature-joint laxity syndrome	Pathogenic (-)
8-143816575-A-T		8q24.3 microdeletion syndrome	Likely pathogenic (Jul 01, 2023)
8-143816594-A-T			Uncertain significance (Nov 10, 2022)
8-143816612-GGATGGCCTTAT-G			Likely pathogenic (Jan 19, 2017)
8-143816630-C-G		PUF60-related disorder	Uncertain significance (Jun 14, 2023)
8-143816630-C-CA		8q24.3 microdeletion syndrome	Pathogenic (Dec 10, 2018)
8-143816631-A-G			Benign/Likely benign (Mar 01, 2023)
8-143816635-G-A		Inborn genetic diseases	Likely benign (Jan 23, 2023)
8-143816641-GA-G		8q24.3 microdeletion syndrome	Likely pathogenic (Jun 26, 2018)
8-143816646-C-T		PUF60-related disorder	Likely benign (Jun 29, 2020)
8-143816650-A-C		8q24.3 microdeletion syndrome	Likely pathogenic (Jan 01, 2022)
8-143816705-AGAT-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 04, 2019)
8-143816711-T-C		8q24.3 microdeletion syndrome • Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
8-143816728-C-T			Likely pathogenic (Jan 19, 2017)
8-143816729-C-T		8q24.3 microdeletion syndrome	Pathogenic/Likely pathogenic (Sep 23, 2022)
8-143816741-A-G		8q24.3 microdeletion syndrome	Likely pathogenic (-)
8-143816741-ACTC-A		Inborn genetic diseases	Uncertain significance (Mar 13, 2024)
8-143816752-A-G		8q24.3 microdeletion syndrome	Pathogenic (Dec 21, 2018)
8-143816790-C-T		PUF60-related disorder	Likely benign (Dec 21, 2022)
8-143816801-G-A		PUF60-related disorder	Uncertain significance (Feb 06, 2024)
8-143816801-G-C		Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities	Likely pathogenic (-)
8-143816816-T-C		8q24.3 microdeletion syndrome	Uncertain significance (Oct 18, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PUF60	protein_coding	protein_coding	ENST00000526683	12	13516

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00323	124283	0	5	124288	0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.44	111	342	0.325	0.0000209	3605
Missense in Polyphen		8	63.955	0.12509		686
Synonymous	-2.28	180	145	1.24	0.0000103	1145
Loss of Function	4.33	2	25.7	0.0778	0.00000118	293

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000291	0.0000291
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.0000275	0.0000178
Middle Eastern	0.000111	0.000111
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: DNA- and RNA-binding protein, involved in several nuclear processes such as pre-mRNA splicing, apoptosis and transcription regulation. In association with FUBP1 regulates MYC transcription at the P2 promoter through the core-TFIIH basal transcription factor. Acts as a transcriptional repressor through the core-TFIIH basal transcription factor. Represses FUBP1-induced transcriptional activation but not basal transcription. Decreases ERCC3 helicase activity. Does not repress TFIIH-mediated transcription in xeroderma pigmentosum complementation group B (XPB) cells. Is also involved in pre-mRNA splicing. Promotes splicing of an intron with weak 3'-splice site and pyrimidine tract in a cooperative manner with U2AF2. Involved in apoptosis induction when overexpressed in HeLa cells. Isoform 6 failed to repress MYC transcription and inhibited FIR-induced apoptosis in colorectal cancer. Isoform 6 may contribute to tumor progression by enabling increased MYC expression and greater resistance to apoptosis in tumors than in normal cells. Modulates alternative splicing of several mRNAs. Binds to relaxed DNA of active promoter regions. Binds to the pyrimidine tract and 3'-splice site regions of pre-mRNA; binding is enhanced in presence of U2AF2. Binds to Y5 RNA in association with TROVE2. Binds to poly(U) RNA. {ECO:0000269|PubMed:10606266, ECO:0000269|PubMed:10882074, ECO:0000269|PubMed:11239393, ECO:0000269|PubMed:16452196, ECO:0000269|PubMed:16628215, ECO:0000269|PubMed:17579712}.
• Disease: DISEASE: Verheij syndrome (VRJS) [MIM:615583]: A syndrome characterized by growth retardation, delayed psychomotor development, dysmorphic facial features, and skeletal, mainly vertebral, abnormalities. Additional variable features may include coloboma, renal defects, and cardiac defects. {ECO:0000269|PubMed:24140112}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Spliceosome - Homo sapiens (human);Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.357
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.4

Haploinsufficiency Scores

• pHI: 0.247
• hipred: Y
• hipred_score: 0.775
• ghis: 0.536

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Puf60

Gene ontology

• Biological process: mRNA splicing, via spliceosome;apoptotic process
• Cellular component: nucleoplasm;cell junction
• Molecular function: DNA binding;RNA binding;protein binding;identical protein binding;cadherin binding